Indirect evidence suggests that benign prostatic hypertrophy in man is an endocrine dystrophy and is related to testicular hormone secretions. We are attempting to inhibit both the production of sex steroids and to block their effects at the cellular level with antiandrogens. The emphasis of this work is currently on defining the critical biochemical effects of anti-androgens and estrogens on the biochemical processes in human prostates in both cytoplasm and nucleus that relate to hormonal regulation of prostate growth. Methods to demonstrate these effects will include; (1) in vitro incubation of tissue-labelled sex steroids, separation of cytosol and nuclear fractions and then identification of steroid-protein binding complexes in these compartments by gel filtration; (2) measurement of DHT, T, delta-4-androstenedione, and 5 alpha, 3 alpha, 17 beta-androstanediol in treated and untreated human prostates. We also plan to attempt to predict the response in advanced carcinoma of the prostate to anti-androgen medication by identifying the presence of specific receptor proteins in the cytosol compartment of tumor cells, indicating differentiation and perhaps androgen dependence. It is hopeed that studies of the site of action of various anti-androgens at the cellular level may lead to a rational plan of multiple drug therapy for carcinoma of the prostate which is more effective than single drugs currently being used.